Featured Research

Bacteria Can't Do Their Thing If They Don't Have Cling; Scientists Open Door To Possible New Treatments For Urinary Tract Infections

Date:

November 18, 2002

Source:

Washington University School Of Medicine

Summary:

Clingy bacteria often spell trouble. Scientists at Washington University School of Medicine in St. Louis have discovered how bacteria manufacture hair-like fibers used to cling to the lining of the kidney and bladder where they cause urinary tract infections.

Share This

St. Louis, Nov. 15, 2002 -- Clingy bacteria often spell trouble. Scientists at Washington University School of Medicine in St. Louis have discovered how bacteria manufacture hair-like fibers used to cling to the lining of the kidney and bladder where they cause urinary tract infections (UTIs). The results are published in the Nov. 15 issue of the journal Cell.

Related Articles

"Our findings should lead to new drugs to treat UTIs by blocking the formation of these protein fibers," says study leader Scott J. Hultgren, Ph.D., the Helen Lehbrink Stoever Professor of Molecular Microbiology. "They also should improve our general understanding of how disease-causing bacteria build, fold and secrete proteins that enable them to cause disease."

Hultgren and his laboratory worked in collaboration with Gabriel Waksman, Ph.D., the Roy and Diana Vagelos Professor of Biochemistry and Molecular Biophysics at the School of Medicine, whose laboratory conducted the X-ray crystallography studies showing the structure of the molecules involved in the fiber assembly process. X-ray crystallography reveals the 3-D arrangement of atoms in proteins.

UTIs are the second most common infectious disease in the United States, says Hultgren. Each year they account for 100,000 hospital admissions and 8 million doctor visits. UTIs mainly affect women, about half of whom experience at least one UTI and 20-40 percent of whom develop recurrent infections.

UTIs begin when bacteria gain a foothold on cells lining the kidney or bladder and grow into colonies. They latch onto cells using tiny fibers known as pili. Similar fibers also are produced by bacteria responsible for a variety of gastric, respiratory and other infections.

The fibers are made up of identical individual pieces, or subunits, linked together like plastic snap beads. Earlier work by Hultgren and Waksman found that as each subunit is made within a bacterium, it is joined to another molecule known as a chaperone. Chaperone proteins are found in all living cells and, as their name implies, protect other molecules from trouble. In this case, they shield subunit proteins from interacting with one another at the wrong time and place.

The present study, however, found that the chaperones here also play a key role in fiber assembly. The crystallographic images revealed that each subunit molecule contains a deep groove. The images further showed that an edge of the chaperone molecule fits into this groove and holds it open.

The chaperone-subunit pair then shuttle to a place at the bacterial membrane where pili are assembling. There, the chaperone slips free of the subunit and is replaced by a tail-like strand projecting from another subunit at the base of the growing fiber.

The strand fits into the groove like a hot dog in a bun. With the chaperone no longer holding the groove open, the edge of the "bun" snaps shut around the strand, firmly locking the two subunits together. In this way, the fiber grows longer one "snap bead" at a time.

Discovering that the fibers consist of interlocking tails explains why bacterial pili are so durable and able to resist harsh conditions in the laboratory, says Hultgren.

The researchers now are working to develop a drug that will block the fiber-assembly process. Without pili to help them cling to cells, the bacteria could be swept more readily from the urinary tract and prevented from forming colonies.

"This collaboration is an example of microbiology, biochemistry and structural biology coming together in a beautiful and complementary fashion," says Waksman. "As a result, we now have a much better idea of how bacteria produce pili, and that knowledge may lead to new and better treatments for UTIs and other bacterial diseases."

Washington University School Of Medicine. "Bacteria Can't Do Their Thing If They Don't Have Cling; Scientists Open Door To Possible New Treatments For Urinary Tract Infections." ScienceDaily. ScienceDaily, 18 November 2002. <www.sciencedaily.com/releases/2002/11/021115070154.htm>.

Washington University School Of Medicine. (2002, November 18). Bacteria Can't Do Their Thing If They Don't Have Cling; Scientists Open Door To Possible New Treatments For Urinary Tract Infections. ScienceDaily. Retrieved March 3, 2015 from www.sciencedaily.com/releases/2002/11/021115070154.htm

Washington University School Of Medicine. "Bacteria Can't Do Their Thing If They Don't Have Cling; Scientists Open Door To Possible New Treatments For Urinary Tract Infections." ScienceDaily. www.sciencedaily.com/releases/2002/11/021115070154.htm (accessed March 3, 2015).

Mar. 3, 2015 — By examining the forces that the segments of mosquito legs generate against a water surface, researchers have unraveled the mechanical logic that allows the mosquitoes to walk on water, which may ... full story

Mar. 3, 2015 — Pediatric otolaryngologists and surgeons are concerned with parents getting the wrong message regarding the safety/desirability of letting babies and young children eat peanuts to prevent them from ... full story

Mar. 3, 2015 — Researchers have developed a new way of rapidly screening yeasts that could help produce more sustainable biofuels. The new technique could also be a boon in the search for new ways of deriving ... full story

Mar. 3, 2015 — Similar to humans and animals, plants possess an innate immune system that protects them from invading pathogens. Molecular structures that only occur in pathogens enable their recognition and ... full story

Mar. 3, 2015 — For almost a century, scientists have been puzzled by a process that is crucial to much of the life in Earth's oceans: Why does calcium carbonate, the tough material of seashells and corals, ... full story

Mar. 3, 2015 — To simulate chimp behavior, scientists created a computer model based on equations normally used to describe the movement of atoms and molecules in a confined space. An interdisciplinary research ... full story

Mar. 3, 2015 — Rather than just waiting patiently for any pollinator that comes their way to start the next generation of seeds, some plants appear to recognize the best suitors and 'turn on' to increase the chance ... full story

Featured Videos

Rare Goblin Shark Found in Australia

AFP (Mar. 3, 2015) — A goblin shark, a rare sea creature described as an &apos;alien of the deep&apos; is found off Australia and delivered to the Australian Museum in Sydney. Duration: 01:25
Video provided by AFP

Zookeepers Copy Animal Poses In Hilarious Viral Photos

Buzz60 (Mar. 2, 2015) — Zookeepers at the Symbio Wildlife Park in Helensburgh, Australia decided to take some of their favorite animal photos and recreate them by posing just like the animals. Jen Markham (@jenmarkham) has the story.
Video provided by Buzz60

Related Stories

Sep. 17, 2014 — The most common type of hospital-associated infection may be preventable with a vaccine, new research in mice suggests. The experimental vaccine prevented urinary tract infections associated with ... full story

June 19, 2013 — Estrogen stimulates the production of the body’s own antibiotic and strengthens the cells in the urinary tract, according to a new study. The results show that estrogen supplements may help ... full story

July 8, 2012 — Humans have known for centuries that copper is a potent weapon against infection. New research shows that the bacteria that cause serious urinary tract infections “know” this, too, and steal ... full story

Apr. 15, 2011 — Urinary tract infections are common in women and occur frequently, affecting 2 to 3 percent of all women. A depletion of vaginal lactobacilli, a type of bacteria, is associated with urinary tract ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.